Dronabinol for Postoperative Pain

(dronabinol Trial)

Overseen By Rose Johnson

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Colorado Joint Replacement

Must be taking: Dronabinol

Must not be taking: Narcotics, Cannabis

Disqualifiers: Depression, Anxiety, Bipolar, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 4 weeks

460 Participants Needed

Trial Summary

Do I need to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have used narcotics in the past 6 weeks or cannabis regularly in the past 3 months. Also, you must be able to take the standardized pain medications like Tylenol, gabapentin, and meloxicam.

What data supports the idea that Dronabinol for Postoperative Pain is an effective treatment?

The available research shows that Dronabinol does not effectively reduce postoperative pain. In a study with 40 women who had surgery, those who took Dronabinol did not experience less pain compared to those who took a placebo. There were no significant differences in pain relief or the time before they needed more pain medication. This suggests that Dronabinol is not effective for managing postoperative pain. ^{1 2 3 4 5}

What safety data exists for Dronabinol in treating pain?

Dronabinol has been evaluated in several clinical trials for its safety profile. A systematic review and meta-analysis found that dronabinol is associated with higher frequencies of dry mouth, dizziness, and headache compared to placebo, but these adverse events are typically mild-to-moderate and transient. In a study on chronic pain patients using opioids, dronabinol was found to provide additional analgesia with dose-related side effects. Another trial in neuropathic pain patients with multiple sclerosis showed that while adverse reactions were initially higher with dronabinol compared to placebo, they decreased with long-term use, and no significant signs of drug abuse or dependency were observed. Overall, dronabinol is considered a safe long-term treatment option, with the most common side effect being dizziness. ^{1 3 6 7 8}

Is the drug Dronabinol a promising treatment for postoperative pain?

Based on the research, Dronabinol does not show evidence of being effective for relieving postoperative pain. In a study with women who had surgery, Dronabinol did not significantly reduce pain compared to a placebo. ^{1 2 3 4 9}

What is the purpose of this trial?

The primary purpose of this study was to determine if cannabinoid use decreases narcotic consumption in patients undergoing total knee arthroplasty (TKA).

Research Team

Jason Jennings, MD

Principal Investigator

Colorado Joint Replacement

Eligibility Criteria

This trial is for adults aged 21-75 undergoing knee replacement at Colorado Joint Replacement who can take oral meds and follow the study plan. They must not have used narcotics in the last 6 weeks, cannabis regularly in the past 3 months, or tobacco recently. No history of major mental disorders, seizures, drug/alcohol abuse, or allergies to dronabinol.

Inclusion Criteria

I am a man who can father children and will use contraception.

I am willing and able to follow all study rules and attend all visits.

I am between 21 and 75 years old.

Exclusion Criteria

You are currently taking another experimental medication.

You have a documented mental illness like bipolar disorder or schizophrenia.

You have had allergic reactions to the ingredients in dronabinol.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Dronabinol or a placebo for 4 weeks post-operatively

4 weeks

Participants take study drug 2 times a day

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Outcome measures collected at 4 and 6 weeks post-operative

Treatment Details

Interventions

• Dronabinol
• Placebo

Trial Overview The trial tests if Dronabinol reduces painkiller needs after knee surgery compared to a placebo. Participants are randomly assigned to receive either Dronabinol or a placebo and their narcotic consumption post-surgery is monitored.

Participant Groups

Group I: dronabinol Experimental Treatment 1 Intervention

Patient will be directed to take 2.5mg of Study Drug 2 times a day for 4 weeks. Patient is blinded as to whether or not this is Dronabinol.

Group II: placebo Placebo Group 1 Intervention

Patient will be directed to take 2.5mg of Study Drug 2 times a day for 4 weeks. Patient is blinded as to whether or not this is Dronabinol.

Dronabinol is already approved in United States, Canada for the following indications:

Approved in United States as Marinol for:

• HIV/AIDS-induced anorexia
• Chemotherapy-induced nausea and vomiting
• Sleep apnea

Approved in United States as Syndros for:

• HIV/AIDS-induced anorexia
• Chemotherapy-induced nausea and vomiting

Approved in Canada as REDUVO for:

• HIV/AIDS-induced anorexia
• Chemotherapy-induced nausea and vomiting

Who Is Running the Clinical Trial?

Colorado Joint Replacement

Lead Sponsor

Trials

13

Recruited

3,300+

Findings from Research

Dronabinol (Δ9-THC) shows potential as an analgesic for chronic pain, but its effectiveness varies due to different pain mechanisms, highlighting the need for a deeper understanding of how it works in the body.

The review emphasizes the importance of developing objective biomarkers to assess the effects of dronabinol on pain, which could help identify which patients are likely to benefit from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dronabinol and chronic pain: importance of mechanistic considerations. de Vries, M., van Rijckevorsel, DC., Wilder-Smith, OH., et al.[2018]

In a study involving 24 multiple sclerosis (MS) patients, dronabinol (delta-9-tetrahydrocannabinol) significantly reduced spontaneous pain intensity compared to a placebo, indicating its potential analgesic effect.

Although the reduction in pain was modest, the findings suggest that dronabinol could be a valuable option for managing central pain in MS patients, a condition that is often challenging to treat.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of the synthetic cannabinoid dronabinol on central pain in patients with multiple sclerosis--secondary publication]. Svendsen, KB., Jensen, TS., Bach, FW.[2013]

In a study involving 30 patients on opioids for chronic pain, dronabinol (synthetic THC) was found to significantly reduce pain intensity and increase treatment satisfaction compared to a placebo, indicating its potential as an effective adjuvant treatment.

The extended Phase II trial showed that titrated doses of dronabinol provided significant pain relief and reduced pain bothersomeness, although side effects were dose-related, suggesting careful monitoring is needed when using this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. Narang, S., Gibson, D., Wasan, AD., et al.[2013]

In a study involving 40 women after abdominal hysterectomy, a single dose of 5 mg oral delta-9-THC did not show significant analgesic effects compared to a placebo, as measured by pain intensity scores at 6 hours post-administration.

While delta-9-THC did not provide pain relief, it was associated with increased awareness of surroundings in 40% of patients, compared to only 5% in the placebo group, indicating a potential psychoactive effect without analgesic benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of analgesic efficacy of oral delta-9-tetrahydrocannabinol in postoperative pain. Buggy, DJ., Toogood, L., Maric, S., et al.[2019]

This study is the first randomized controlled trial to evaluate the effectiveness of dronabinol, a form of Δ9-THC, in reducing opioid consumption in adults with traumatic injuries, involving 122 participants over a 48-hour treatment period.

The trial aims to determine if adding dronabinol to standard pain management can lower the amount of opioids needed, potentially offering a safer alternative for pain relief in acute injury situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Dronabinol for Acute Pain Management in Adults with Traumatic Injury: Study Protocol of A Randomized Controlled Trial. Swartwood, C., Salottolo, K., Madayag, R., et al.[2020]

In a meta-analysis of 16 trials, nabilone was associated with significantly higher rates of drowsiness, dizziness, and dry mouth compared to placebo, indicating a notable risk of these side effects.

Dronabinol also showed increased occurrences of dry mouth, dizziness, and headache compared to placebo, but the overall severity of adverse events was generally mild-to-moderate, suggesting that the benefits may outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials. Bajtel, Á., Kiss, T., Tóth, B., et al.[2022]

In a clinical trial involving 240 multiple sclerosis patients over 16 weeks, dronabinol reduced neuropathic pain intensity by 1.92 points, similar to the 1.81 points reduction seen with placebo, indicating no significant difference in pain relief between the two treatments.

Dronabinol was found to be a safe long-term treatment option, with a higher rate of adverse reactions compared to placebo (50% vs. 25.9%), but these reactions decreased to 26% during extended use, and there were no significant signs of drug abuse or dependency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dronabinol Is a Safe Long-Term Treatment Option for Neuropathic Pain Patients. Schimrigk, S., Marziniak, M., Neubauer, C., et al.[2018]

Cannabis-derived medications like dronabinol and nabilone are effective for treating nausea and vomiting from chemotherapy and appetite loss in AIDS patients, while medical cannabis is commonly recommended for pain and muscle spasms, showing significant improvement in these conditions.

While the adverse effects of cannabis are generally mild, such as dizziness, there are serious safety concerns, particularly regarding adolescent use leading to increased schizophrenia risk and cognitive impairments, as well as risks of accidental ingestion in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacologic and clinical effects of medical cannabis. Borgelt, LM., Franson, KL., Nussbaum, AM., et al.[2022]

In a study of 19 patients with refractory neuropathic pain, 75% of those who continued dronabinol treatment for over 3 months reported an improvement in their health, suggesting its potential efficacy as a pain management option.

However, 74% of patients experienced at least one adverse event, with six needing to discontinue treatment, highlighting the importance of careful monitoring and evaluation of the drug's safety and benefit-risk balance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of dronabinol in the treatment of resistant neuropathic pain: Feedback from patients followed in a multidisciplinary pain center]. Richet, E., Ferret, L., Gaboriau, L., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Dronabinol and chronic pain: importance of mechanistic considerations. [2018]

2. Denmark pubmed.ncbi.nlm.nih.gov

[Effect of the synthetic cannabinoid dronabinol on central pain in patients with multiple sclerosis--secondary publication]. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Lack of analgesic efficacy of oral delta-9-tetrahydrocannabinol in postoperative pain. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of Dronabinol for Acute Pain Management in Adults with Traumatic Injury: Study Protocol of A Randomized Controlled Trial. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Dronabinol Is a Safe Long-Term Treatment Option for Neuropathic Pain Patients. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

The pharmacologic and clinical effects of medical cannabis. [2022]

9. France pubmed.ncbi.nlm.nih.gov

[Use of dronabinol in the treatment of resistant neuropathic pain: Feedback from patients followed in a multidisciplinary pain center]. [2023]